title: Tracing the tracks of genotoxicity by trivalent and hexavalent chromium in Drosophila melanogaster.
abstract: Mutagen sensitive strains (mus) in Drosophila are known for their hypersensitivity to mutagens and environmental carcinogens. Accordingly, these mutants were grouped in pre- and post-replication repair pathways. However, studying mutants belonging to one particular repair pathway may not be adequate for examining chemical-induced genotoxicity when other repair pathways may neutralize its effect. To test whether both pre-and post-replication pathways are involved and effect of Cr(III)- and Cr(VI)-induced genotoxicity in absence or presence of others, we used double mutant approach in D. melanogaster. We observed DNA damage as evident by changes in Comet assay DNA migration in cells of larvae of Oregon R(+) and single mutants of pre- (mei-9, mus201 and mus210) and post- (mei-41, mus209 and mus309) replication repair pathways and also in double mutants of different combinations (pre-pre, pre-post and post-post replication repair) exposed to increasing concentrations of Cr(VI) (0.0, 5.0, 10.0 and 20.0 μg/ml) for 48 h. The damage was greater in pre-replication repair mutants after exposure to 5.0 μg/ml Cr(VI), while effects on Oregon R(+) and post replication repair mutants were insignificant. Post-replication repair mutants revealed significant DNA damage after exposure to 20.0 μg/ml Cr(VI). Further, double mutants generated in the above repair categories were examined for DNA damage following Cr(VI) exposure and a comparison of damage was studied between single and double mutants. Combinations of double mutants generated in the pre-pre replication repair pathways showed an indifferent interaction between the two mutants after Cr(VI) exposure while a synergistic interaction was evident in exposed post-post replication repair double mutants. Cr(III) (20.0 μg/ml) exposure to these strains did not induce any significant DNA damage in their cells. The study suggests that both pre- and post-replication pathways are affected in Drosophila by Cr(VI) leading to genotoxicity, which may have consequences for metal-induced carcinogenesis.
authors.affiliation: Embryotoxicology Section, Indian Institute of Toxicology Research, Lucknow 226 001, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Mishra
authors.forename: Anurag
authors.initials: A
authors.lastname: Sharma
authors.forename: M P S
authors.initials: MP
authors.lastname: Negi
authors.forename: U N
authors.initials: UN
authors.lastname: Dwivedi
authors.forename: D Kar
authors.initials: DK
authors.lastname: Chowdhuri
mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004331:Drosophila melanogaster / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*
chemical_list: D002274:Carcinogens, Environmental; D009153:Mutagens; D002857:Chromium; C074702:chromium hexavalent ion